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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease.
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Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease.

机译：阿尔茨海默氏病转基因小鼠模型中兴奋性毒性和前列腺素代谢的变化。

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To address the potential impact of presenilin mutations on the prostaglandin metabolism in a neurodegenerative model of glutamatergic excitotoxicity, we injected kainic acid intraperitoneally (30mg/kg body weight) into mice over-expressing the human N141I mutation of presenilin-2, which is known to cause an early-onset form of Alzheimer's disease. We compared the seizure activity as well as seizure lethality in 2- and 6-month-old mice, transgenic for the above-mentioned point mutation, and their wildtype littermates and found that mice harboring the hN141I mutation showed a relative resistance to excitotoxic treatment. This was associated with a constituitively reduced expression of the cyclooxygenases COX-1 and COX-2 in the hippocampus of N141I presenilin-2 mice and a reduced induction of COX-2 expression post-kainate injection. In the past, clinical trials have suggested that both non-steroidal anti-inflammatory drugs, which impact upon a cell's prostaglandin metabolism, and glutamatergic antagonists might be of benefit to patients suffering from Alzheimer's-type dementias. Yet, the exact mechanism by which these drugs are beneficial remains unclear, although it seems possible that presenilins might be implicated in the process, at least in the case of early-onset forms. The data presented here strongly support the notion of an implication of presenilins in the alterations in the prostaglandin system, which have been observed in Alzheimer's disease and may contribute to the underlying pathogenesis of the disease.
机译：为了解决谷氨酸能兴奋性神经退行性模型中早老素突变对前列腺素代谢的潜在影响，我们向过表达人类早老素2的N141I突变的小鼠腹膜内注射海藻酸（30 mg / kg体重）。会导致阿尔茨海默氏病的早期发作。我们比较了转基因的上述点突变的2个月和6个月大小鼠的癫痫发作活性以及癫痫发作致死率，以及它们的野生型同窝仔，发现带有hN141I突变的小鼠表现出对兴奋性毒性治疗的相对抗性。这与N141I早老素2小鼠海马中的环氧合酶COX-1和COX-2的组成性表达降低以及海藻酸盐注射后COX-2表达的诱导降低有关。过去，临床试验表明，影响细胞前列腺素代谢的非甾体类抗炎药和谷氨酸能拮抗剂都可能对患有阿尔茨海默氏型痴呆症的患者有益。然而，尽管似乎早老蛋白可能参与了这一过程，但至少在早发形式的情况下，似乎尚不清楚这些药物有益的确切机制。本文提供的数据强烈支持早老素在前列腺素系统改变中的意义，这在阿尔茨海默氏病中已观察到，可能有助于该病的潜在发病机理。

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